1. Field of the Invention:
This invention relates to dipeptidyl 4-0, 6-0 acyl-2-amino 2 deoxy-D-glucoses which alone, or in combination with an anti AIDS drug, e.g. azidothymidine, protect against opportunistic, bacterial, fungal or viral infection in a human host, immunocompromised by an AIDS-related virus.
2. Brief Description of Disclosures in the Art
The search for new immunostimulants capable of augmenting host defenses to combat infection, cancer and congenital immunodeficiency disorders is an increasingly important area of pharmaceutical endeavor particularly as it relates to AIDS related viruses.
Seven years ago few had ever heard of acquired immune deficiency syndrome, or AIDS. This puzzling affliction, then seen in only a small number of young, homosexual men, was something new and unnamed. Today, it's hard to find anyone in the U.S. who hasn't heard of AIDS, the disease that can debilitate and then kill its victim with horrific swiftness.
AIDS has come to be recognized as a public health emergency. More than 27,700 American men, women, and children have been stricken by it; the death toll is 16,000 and rising. The U.S. Public Health Service predicts that by the end of 1991 more than 179,000 persons will have succumbed to the disease.
Thus far, there is no cure for AIDS.
Technically, acquired immune deficiency syndrome (AIDS) is a transmissible deficiency of cellular immunity characterized by opportunistic infections and certain rare malignancies. The dominant risk groups for AIDS include homosexually active males, intravenous drug abusers, recipients of transfusions and blood products, and the heterosexual partners and children of high-risk individuals, suggesting the involvement of an infectious agent transmitted through intimate contact or blood products.
Recent evidence indicates that the infectious agent responsible for disease transmission is a novel lymphotropic retrovirus, currently designated HIV I (human immunodeficiency virus) and also known as lymphadenopathy-associated virus (LAV) (Barre-Sinoussi et al., Science 220: 868 (1983)). Similar viruses have been reported by other scientific groups (Popovic et al., Science 224: 497 (1984); Levy et al. Science 225: 840 (1984)) and designated human T cell lymphotropic virus type III (HTLV-III), AIDS-associated retrovirus (ARV), or immune deficiency associated virus (IDAV). Still more recent data indicates that LAV, HTLV III, ARV and IDAV share several important characteristics, including substantial nucleotide homology (Wain-Hobson et al., Cell 40: 9 (1985); Muesing et al., Nature 313: 450 (1985); Sanchez-Pescador et al., Science 227: 484 (1985)), and should be considered isolates of the same virus, although there is a likelihood that strain to-strain variations among the viral isolates will exist. In addition to exhibiting substantial nucleotide homology, the isolates are similar with respect to morphology, cytopathology, requirements for optimum reverse transcriptase activity, and at least some antigenic properties (Levy, supra: Schupbach et al., Science 224: 503 (1984)). The above materials are hereby incorporated by reference to characterize the phrase "AIDS-related virus".
U.S. Pat. No. 4,368,190 to Shen et al. (assigned to Merck & Co. Inc.) describes immunologically active depeptidyl 4-0, 6 0 acyl 2 amino 2-deoxy-D-glucoses described herein and their methods of preparation, which reference is hereby incorporated by reference for this particular purpose.
However, the above disclosure does not specifically describe the use of the compounds alone, or in combination with an anti AIDS drug, e.g. azidothymidine, for use as host resistance enhancing agents, i.e., immunostimulators, specifically to combat opportunistic viral, fungal, bacterial infections in AIDS-immunocompromised hosts.